AUTHOR=Tan Xinrui , Pan Xiongfeng , Wu Xiaochuan , Zheng Songjia , Chen Yuyao , Liu Donghai , Zhang Xingxing 

TITLE=Glucagon-like peptide-1 receptor agonists as add-on therapy to insulin for type 1 diabetes mellitus

JOURNAL=Frontiers in Pharmacology

VOLUME=14

YEAR=2023

URL=https://www.frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2023.975880

DOI=10.3389/fphar.2023.975880

ISSN=1663-9812

ABSTRACT=<p><bold>Background:</bold> To assess the efficacy and safety of glucagon-like peptide-1 receptor agonists (GLP-1 RAs) used as an adjunct to insulin therapy in adults with type 1 diabetes.</p><p><bold>Methods:</bold> A search of electronic databases (Medline, Embase, and the Cochrane Central Register of Controlled Trials) from 1 January 1950 to 23 May 2021 was conducted to find randomized controlled trials. The primary outcome was the change in HbA1c. Eight efficacy and six safety secondary endpoints were evaluated <italic>via</italic> meta-analysis. Weighted mean difference (WMD) and odds ratio (OR), alongside 95% confidence interval (CI), were calculated using the random effects model.</p><p><bold>Results:</bold> Among 1,379 candidate studies, 11 trials comprising 2,856 participants satisfied the inclusion criteria. Overall, GLP-1 RA adjunctive therapy reduced HbA1c by −0.21% (95% CI, −0.33 to −0.10), weight by −4.04 kg (−4.8 to −3.27), systolic pressure by −2.57 mmHg (−4.11 to −1.03), and diastolic blood pressure by −1.02 mmHg (−1.99 to −0.06). In addition, there was a decrease in prandial insulin dose (WMD, −4.23 IU; 95% CI, −5.26 to −3.20), basal insulin dose (−2.40 IU; −3.93 to −0.87), and total insulin dose (−5.73 IU; −10.61 to −0.86). Moreover, GLP-1 RAs did not increase the incidence of severe hypoglycemia, diabetic ketoacidosis, or severe adverse events. However, GLP-1 RAs increased the incidence of gastrointestinal adverse events (OR, 2.96; 95% CI, 2.33–3.77).</p><p><bold>Conclusion:</bold> Our meta-analysis of randomized clinical trials suggests moderate beneficial effects of GLP-1 RAs on the metabolic profile in patients with type 1 diabetes, without an increased risk of serious adverse events.</p><p><bold>Clinical Trial Registration:</bold><ext-link ext-link-type="uri" xlink:href="https://www.crd.york.ac.uk/PROSPERO" xmlns:xlink="http://www.w3.org/1999/xlink">https://www.crd.york.ac.uk/PROSPERO</ext-link>; Identifier: CRD 42020199840.</p>